Adding misoprostol to oxytocin immediately after childbirth did not additionally prevent postpartum hemorrhage and may have increased women’s risks for adverse events compared with administering oxytocin alone, according to a new randomized controlled trial. The study was halted early because of the findings.
“All in all, the findings of this trial do not support the use of misoprostol in addition to oxytocin for the prevention of postpartum hemorrhage,” the authors write. “[D]espite misoprostol’s ready availability, easy use, and utility for other pregnancy indications, oxytocin should remain the mainstay of prophylaxis of postpartum hemorrhage in high-income countries, and misoprostol should be used infrequently for this indication.”
Thibaud Quibel, MD, from the Department of Obstetrics and Gynecology, Poissy-Saint Germain Hospital, France, and colleagues report their findings online September 8 in Obstetrics & Gynecology.
Other research had suggested the two drugs might work synergistically. “We hypothesized that a combination of routine oxytocin and misoprostol, compared with oxytocin alone, both as part of active management of the third stage of labor, would decrease the postpartum hemorrhage rate,” the researchers explain.
The study included women aged at least 18 years for whom a vaginal delivery was anticipated, who were in the first stage of labor, who were at 36 to 42 weeks of gestation, who had epidural anesthesia in place, and who had provided written informed consent for participation in the study. The study excluded women with multiple pregnancies, known hypersensitivity to prostaglandins, cesarean delivery, or participation in another clinical trial.
The researchers randomly assigned women during the first stage of labor in a one-to-one ratio to receive 400 μg misoprostol or placebo immediately after the baby’s birth.
All women received active management of the third stage of labor, including a prophylactic intravenous injection of 10 IU oxytocin after the delivery of the baby’s anterior shoulder, early umbilical cord clamping, and controlled cord traction.
“Monitoring of blood loss started as soon as the neonate was born and before delivery of the placenta. Blood loss was collected into a calibrated plastic bag placed under the mother’s pelvis. The transparent, graduated bag allowed continuous monitoring of blood loss and was maintained in place for at least 2 hours after the neonate’s delivery,” the authors write.
The baseline characteristics were similar in the two groups of women, as were the birth weights of the infants. There was no significant difference in the primary outcome of postpartum hemorrhage greater than 500 mL within 2 hours of birth (8.4% [68/806] in the misoprostol vs 8.3% [66/797] in the placebo group; P = .98). The rates of severe postpartum hemorrhage (postpartum hemorrhage >1000 mL within 2 hours after birth) were also similar, at 1.8% and 2.4%, respectively (P = .57).
Maternal adverse events were significantly more frequent in the women who received misoprostol (fever, 30.4% vs 6.3% in the placebo group [P < .001]; shivering, 10.8% vs 0.6% [P < .001]). Nausea (2.7% vs 1.0%), vomiting (2.2% vs 0.8%), and diarrhea (0.7% vs 0%) were also significantly more frequent among women in the misoprostol group than those in the placebo group.
“Although misoprostol may be useful in settings with poor health services where availability of both refrigerators and skilled birth attendants is scarce, its use should be infrequent in high-income countries, especially combined with oxytocin. This is especially true in that misoprostol induces numerous and frequent maternal side effects,” the authors conclude. “Given that misoprostol is routinely used prophylactically among a very large number of healthy women, the greatest emphasis should be placed on limiting its use in high-income countries. Continued monitoring for adverse effects is essential.”
The authors have disclosed no relevant financial relationships.
Obstet Gynecol. 2016;128:805-811.
Brown, T. Oxytocin Without Misoprostol Best for Postpartum Hemorrhage Prevention. Medscape, 09 Sep 2016. Retrieved from http://www.medscape.com/viewarticle/868601